US8815892B2ActiveUtilityA1
P2X7R antagonists and their use
Est. expiryMar 25, 2028(~1.6 yrs left)· nominal 20-yr term from priority
Inventors:Michael Bos
C07D 403/06A61K 31/41C07D 471/04A61K 31/404C07D 209/42C07D 231/56
42
PatentIndex Score
0
Cited by
52
References
16
Claims
Abstract
The present application is directed to novel P2X7R antagonists that are indol-3-carboxamide or azaindole-3-carboxamide compounds, pharmaceutical compositions comprising the same and their use for the prophylactic or therapeutic treatment of diseases mediated by P2X7R activity.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A method for treating multiple sclerosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of compound of formula (I):
wherein
R 1 is a cycloheptylmethyl, cycloheptylethyl, bicyclo[2.2.2]octan-1-ylmethyl, or bicyclo[2.2.2]octan-1-ylethyl group;
R 2 is selected from straight or branched C 1 -C 5 alkyl which may optionally substituted with —OH, C 1 -C 5 alkoxy, NH 2 —, N(R a ) 2 —, NHR a —, CN—, CF 3 , halogen, piperidino, morpholino, pyrrolidino, 5H-tetrazolylpropyl, methylcarbamoyl, dimethylcarbamoyl, or ethylmethylcarbamoyl, wherein Ra is hydrogen or C 1 -C 5 alkyl;
R 3 , R 4 , R 5 , R 6 are at each occurrence independently selected from hydrogen, halogen, methyl, hydroxy, methoxy, cyano, or trifluoromethyl; and
a, b, c, d, x are carbon;
or a pharmaceutically acceptable salt or solvate thereof.
2. A method according to claim 1 , wherein R 1 is bicyclo[2.2.2]octan-1-ylmethyl or bicyclo[2.2.2]octan-1-ylethyl.
3. A method according to claim 1 , wherein R 2 is C 1 -C 5 alkyl or C 2 -C 5 hydroxyalkyl.
4. A method according to claim 1 , wherein at least two of R 3 , R 4 , R 5 and R 6 are hydrogen.
5. A method for treating neuropathic pain, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of compound of formula (I):
wherein
R 1 is a cycloheptylmethyl, cycloheptylethyl, bicyclo[2.2.2]octan-1-ylmethyl, or bicyclo[2.2.2]octan-1-ylethyl group;
R 2 is selected from straight or branched C 1 -C 5 alkyl which may optionally substituted with —OH, C 1 -C 5 alkoxy, NH 2 —, N(R a ) 2 —, NHR a —, CN—, CF 3 , halogen, piperidino, morpholino, pyrrolidino, 5H-tetrazolylpropyl, methylcarbamoyl, dimethylcarbamoyl, or ethylmethylcarbamoyl, wherein Ra is hydrogen or C 1 -C 5 alkyl;
R 3 , R 4 , R 5 , R 6 are at each occurrence independently selected from hydrogen, halogen, methyl, hydroxy, methoxy, cyano, or trifluoromethyl; and
a, b, c, d, x are carbon;
or a pharmaceutically acceptable salt or solvate thereof.
6. A method according to claim 5 , wherein R 1 is bicyclo[2.2.2]octan-1-ylmethyl or bicyclo[2.2.2]octan-1-ylethyl.
7. A method according to claim 5 , wherein R 2 is C 1 -C 5 alkyl or C 2 -C 5 hydroxyalkyl.
8. A method according to claim 5 , wherein at least two of R 3 , R 4 , R 5 and R 6 are hydrogen.
9. A method for treating osteoporosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of compound of formula (I):
wherein
R 1 is a cycloheptylmethyl, cycloheptylethyl, bicyclo[2.2.2]octan-1-ylmethyl, or bicyclo[2.2.2]octan-1-ylethyl group;
R 2 is selected from straight or branched C 1 -C 5 alkyl which may optionally substituted with —OH, C 1 -C 5 alkoxy, NH 2 —, N(R a ) 2 —, NHR a —, CN—, CF 3 , halogen, piperidino, morpholino, pyrrolidino, 5H-tetrazolylpropyl, methylcarbamoyl, dimethylcarbamoyl, or ethylmethylcarbamoyl, wherein Ra is hydrogen or C 1 -C 5 alkyl;
R 3 , R 4 , R 5 , R 6 are at each occurrence independently selected from hydrogen, halogen, methyl, hydroxy, methoxy, cyano, or trifluoromethyl; and
a, b, c, d, x are carbon;
or a pharmaceutically acceptable salt or solvate thereof.
10. A method according to claim 9 , wherein R 1 is bicyclo[2.2.2]octan-1-ylmethyl or bicyclo[2.2.2]octan-1-ylethyl.
11. A method according to claim 9 , wherein R 2 is C 1 -C 5 alkyl or C 2 -C 5 hydroxyalkyl.
12. A method according to claim 9 , wherein at least two of R 3 , R 4 , R 5 and R 6 are hydrogen.
13. A method for treating rheumatoid arthritis, chronic obstructive pulmonary disease, glaucoma, amyotrophic lateral sclerosis, Parkinson's disease, or Alzheimer disease, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of compound of formula (I):
wherein
R 1 is a cycloheptylmethyl, cycloheptylethyl, bicyclo[2.2.2]octan-1-ylmethyl, or bicyclo[2.2.2]octan-1-ylethyl group;
R 2 is selected from straight or branched C 1 -C 5 alkyl which may optionally substituted with —OH, C 1 -C 5 alkoxy, NH 2 —, N(R a ) 2 —, NHR a —, CN—, CF 3 , halogen, piperidino, morpholino, pyrrolidino, 5H-tetrazolylpropyl, methylcarbamoyl, dimethylcarbamoyl, or ethylmethylcarbamoyl, wherein Ra is hydrogen or C 1 -C 5 alkyl;
R 3 , R 4 , R 5 , R 6 are at each occurrence independently selected from hydrogen, halogen, methyl, hydroxy, methoxy, cyano, or trifluoromethyl; and
a, b, c, d, x are carbon;
or a pharmaceutically acceptable salt or solvate thereof.
14. A method according to claim 13 , wherein R 1 is bicyclo[2.2.2]octan-1-ylmethyl or bicyclo[2.2.2]octan-1-ylethyl.
15. A method according to claim 13 , wherein R 2 is C 1 -C 5 alkyl or C 2 -C 5 hydroxyalkyl.
16. A method according to claim 13 , wherein at least two of R 3 , R 4 , R 5 and R 6 are hydrogen.Join the waitlist — get patent alerts
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